Pleural Effusion Formation Linked to Altered Transporter Expression Involved in Alveolar Fluid Clearance: Insights From the Monocrotaline Model of Pulmonary Hypertension

Pleural effusions (PLEF) in pulmonary arterial hypertension (PAH), particularly in patients with isolated right heart failure, are associated with poor prognosis and increased mortality. This study investigates changes in alveolar fluid clearance (AFC) transporter expression in relation to lung fluid accumulation and PLEF formation during PAH progression, as well as the effects of terbutaline (TER) and riociguat (RIO) treatment. Using a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model, we performed a detailed molecular analysis of AFC transporter expression at different disease stages, both before and after PH development. Although only minor changes were observed in the early stages prior to PH onset, a downregulation of key transporters, γ-ENaC and Na⁺/K⁺-ATPase subunits Atp1a2 and Atp1b1, was evident in the later stages. This reduction may have contributed to pulmonary oedema, as indicated by histological analysis. TER treatment modestly increased Atp1a2 expression, aligning with the stimulatory effects of β₂-agonist on oedema clearance. Conversely, RIO showed trends towards fluid accumulation, indicated by perivascular oedema in control animals and reduced oxygen saturation in MCT-treated rats. These findings support a potential role of impaired AFC in the pathogenesis of PLEF in PAH and suggest that pharmacological interventions may differentially affect lung fluid homeostasis in this setting.